The ability to raise broadly neutralizing antibodies is likely to be an important component of any effective vaccine against HIV-1. One class of these antibodies has special properties that merit more intensive study: (l) These antibodies have epitopes that are further exposed by binding of gp120 to CD4. (2) They compete with gp120 binding to CCR5 and to CCR5-derived peptides. (3) As we show here, many of these antibodies are, like CCR5, modified by tyrosine sulfate in their gp120-binding domains, and, in the single case characterized, sulfate groups are critical for gp120 binding. (4) As we also demonstrate here, members of this latter group bind with high affinity to envelope glycoproteins of isolates that utilize CCR5, but not those that utilize CXCR4. (5) As we observe here, this class of antibodies has a significant bias toward the use of a single variable chain gene (VH1-69) from approximately forty in the human germline. Collectively, these data suggest that these antibodies can function as mimics of CCR5, and thus may have the potential to neutralize a broad range of primary isolates. Their common variable chain suggests that they associate in a manner similar to HIV-1 gp120, despite differences in their complementarity determining regions (CDRs). Here, we propose to document the presence and functional role of sulfate groups on these antibodies, determine the degree of overlap between the epitopes of these antibodies and the CCR5-binding region of gp120, and explore the basis of observed preference for the VH1-69 variable gene. These studies will provide further insight into the association of gp120 with CCR5 and with this important class of antibodies, and will lay the groundwork for future studies of tyrosine-sulfated antibodies in HIV-1 infected individuals and infected or vaccinated animals.